Grant: Project Grant

Short periods of bedrest rapidly compromises health, as inactivity reduces muscle mass, induces insulin resistance/prediabetes and decreases the hearts ability to pump blood. We aim to utilize a nutritional approach to prevent these negative responses during short-term (7 day) bedrest in humans. We have identified dietary nitrate as a possible clinical tool to mitigate the detrimental effects of physical inactivity. Importantly, nitrate exerts a physiological effect within minutes and therefore can be utilized for unexpected periods of bedrest, and we have generated compelling evidence in rodents that it prevents many of the mechanisms associated with bedrest-induced compromised health. Specifically, we have shown in mice that nitrate prevents markers of muscle mass loss, cellular stress in diverse tissues, prediabetes and heart failure. Given our strong proof-of-principle evidence in rodents that nitrate prevents many of the mechanisms implicated in decreased cardiometabolic health, we aim to translate these findings to a study of human bedrest to test the efficacy and underlying mechanisms-of-action in humans. It is our belief that dietary nitrate will prevent bedrest-induced prediabetes and cardiovascular impairments, which if successful, could be rapidly translated to clinical practice. Completion of this project could therefore provide an inexpensive strategy to improve human health in common situations of injury and illness associated with physical inactivity.